Thirty to up to 70% of all conceptuses are lost spontaneously as pre-implantation embryos. About half of the losses are due to chromosomal abnormalities but for the remainder other explanations have to be sought including an adverse maternal/embryonal microenvironment.

During gametogenesis, gene imprinting patterns inherited from both parents are erased. Transcription of embryonal alleles by demethy lation at CpG sites is initiated as early as the 2- to 4-cell stage and alternates between mono- and bi-allelic expression. Transcription is generalized at early stages of development, but the final tissue-specific CpG methylation pattern is established only post-implantation. Genes transcribed from paternal alleles appear to promote cell proliferation while transcription modifiers are transcribed from maternal alleles. This seems correct at least for genes IGF-2, a major embryonal mitogen, its receptor, for H19 and the WT genes.

Cell differentiation and intercellular communication begins at compaction of the 16-cell morula. Intercellular signaling through extracellular matrix(ECM), adhesion sites, and cytokines regulate gene transcription. The 8-cell morula starts synthesizing is own ECM proteins, integrin and cadherin adhesion molecules, and cytokines including II-1, -6, TGFß, TNF, ß and EGF.

Since the human 8 cell morula has become accessible to biopsy procedures the ontogeny of the microenvironment can now be studied in early pregnancy loss.